Montefiore Einstein Center for Cancer Care, Professor in the Department of Medicine, Department of Developmental and Molecular Biology,

Axicabtagene ciloleucel (axi-cel, Yescarta) is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This cellular therapy has been remarkably effective in DLBCL clinical trials, resulting in high rates of remissions in relapsed and refractory cases.

 The majority of the clinical data for axi-cel, however, have been from people treated in clinical trial settings under tightly regulated follow-up and monitoring. It also excluded people who suffer from neurological symptoms or an elevated white blood cell count in the cerebrospinal fluid, as well as other comorbidities. We wanted to evaluate the safety and efficacy of axi-cel in an innercity tertiary care hospital in the Bronx to see if axi-cel is a viable treatment option for our population.

, with the first 10 patients treated with axi-cel demonstrated the efficacy of this cellular therapy in patients with DLBCL following the FDA approval in a “real-world setting.” 

 Our treatment group included high-risk patients with 8 individuals (80%) having received at least 3 lines of therapy. Six individuals underwent prior radiation and 7 had recurrent disease after prior autologous hematopoietic stem cell transplant. The cohort included 1 person with HIV, 2 with hepatitis B, and 2 people with central nervous system (CNS) lymphoma. Treatment with axi-cel led to significant responses and 8 of 10 patients achieved a complete remission at 3 months. This included individuals with prior CNS involvement (

). Treatment was generally well-tolerated with 20% of patients experiencing grade 2 or higher cytokine release syndrome (CRS). One person each with HIV and hepatitis B responded without significant toxicities.

Figure 1. Response to Treatment after Axicabtagene Ciloleucel (Click to Enlarge)

Figure 2. PET-CT Images of Patients Treated With Axicabtagene Ciloleucel (Click to Enlarge)

Although data from 2 commercially available cellular products, axi-cel and tisagenlecleucel (Kymriah), have shown complete response in 54% of 111 and 40% of 93 people, respectively,

 most of the published data are from clinical trial participants, usually from homogenous populations, so barriers such as concomitant viral infections and neurological disease are not taken into account. Our report showed that axi-cel can be used successfully in ethnically diverse patients at an inner-city hospital with cancer specialists treating people with high-risk disease.

The most concerning adverse events associated with CAR T-cell therapy include CRS, an inflammatory response, which can manifest as a fever, nausea, rapid heartbeat, trouble breathing, and immune effector cell—associated neurotoxicity syndrome (ICANS).

 In this article, our patients experienced fever following treatment with CAR T-cell therapy, which we expected.

All treated patients developed an abnormally low absolute neutrophil count less than 500 cells/μL with a duration of about 6 days and the lowest level of white blood cell count occurring 6 days following infusion. Neutropenic fever occurred in 8 of 10 patients. Lymphocyte depletion was achieved in all patients before treatment with CAR T-cell therapy. The reduction in lymphocytes lasted 2 weeks, with recovery seen at day 12. The average length of hospital stay was 23 days. CRS and ICANS were evaluated and graded per American Society for Transplantation and Cellular Therapy guidelines.

 CRS was observed in 6 patients (grade ≥2 CRS in 2). ICANS was observed in 5 patients (grade ≥3 ICANS in 3). Three patients received tocilizumab (Actemra). Two patients developed 

 colitis, 1 of whom needed a medical intensive care unit stay for hypotension, with requiring 1 vasopressor to increase their blood pressure for less than 48 hours (grade 3 CRS) and eventually had a full recovery.

This report also shows that CD19-directed CAR T-cell therapy can be successfully used in patients positive for HIV and hepatitis B. According to Ira Braunschweig, MD, “Successful achievement of complete responses of refractory lymphoma patients with axi-cel, especially in settings like Montefiore where we have people with various comorbidities, demonstrates that we can broaden the use of this therapy to new populations. It is encouraging to see this treatment be effective for our patients, who have either CNS involvement, HIV and active hepatis B, as these individuals were excluded from clinical trials. We are proud of our transplant physicians, nurses, physician assistants, and house staff who have built an outstanding cell therapy program at Montefiore.” Braunschweig is director of the Stem Cell Transplant Program and the clinical program director of Hematologic Malignancies at Montefiore Einstein Center for Cancer Care and associate professor of Medicine (Oncology) at Albert Einstein College of Medicine.

These results not only add to the mounting evidence of the safety and efficacy of CD19—directed CAR T-cell therapy in patients with aggressive DLBCL who have severe comorbidities such as CNS involvement. The findings also demonstrate that just because someone suffers from HIV or active hepatitis B, that does not mean they need to be excluded from receiving cutting-edge cellular therapies to treat relapsed lymphoma.

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Investigators at Montefiore showed that axicabtagene-ciloleucel can be used successfully in ethnically diverse patients with high-risk, relapsed/refractory diffuse large B-cell lymphoma at an inner-city hospital.

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